In recent years, increased attention has been drawn to the abuse of prescription drugs. The abuse, or non-medicinal use, of prescription medicines has been reported to be an increasing problem particularly in North America. This phenomenon has become an increasing epidemiological, public health and political concern (See, for example, Fischer and Rehm, J. Pain 9:6, 2008 490-493). In 2006, it was reported that 16.2 million Americans age 12 and older had taken a prescription pain reliever, tranquilizer, stimulant, or sedative for nonmedical purposes at least once in the year prior to being surveyed (National Survey on Drug Use and Health; http://www.samhsa.gov/). In another study, it reported that approximately 5.2% of 12th graders abused OxyContin® for nonmedical purposes at least once in the year prior to being surveyed (Monitoring the Future http://www.monitoringthefuture.org/).
Methods for abusing prescription drugs are varied and include, for example, single or multiple step extraction, physical tampering followed by crushing, extraction, melting, volatilization or direct administration. For purposes of abuse, methods of administering drug substances obtained from prescription drug products or of the drug products themselves are similarly diverse and include, for example, injection, smoking, swallowing, sublingual or buccal administration, chewing, and administration as suppository (See, e.g., National Institute of Drug Abuse, 2008). Prescription drug products that typically misused primarily fall into three groups: 1) Opioids prescribed for pain; 2) CNS depressants prescribed for anxiety of sleep problems; and 3) Stimulants, prescribed, for example, for attention deficit hyperactivity, narcolepsy or obesity. In the context of controlled release opioid products, chewing of the drug product to break up and provide rapid release of a relatively large dose of the opioid drug substance is one of the most commonly used methods of abuse.
Because the potential for abuse of prescription drug products has become an important issue for the U.S. Food and Drug Administration (FDA), the pharmaceutical industry is striving to develop abuse resistant formulations in order to reduce the potential for misuse of prescription drugs. Examples of two abuse resistant drug products submitted to the FDA for approval include Remoxy™ and Embeda™. The Remoxy™ product is formulated to be an abuse resistant product for the delivery of oxycodone, while the Embeda™ product is formulated to be an abuse resistant product for the delivery of morphine. The Embeda™ product was approved by the FDA the on the 14th of October, 2009.
Alcohol-induced dose dumping of drug substance from prescription drug products also presents potential abuse and safety problems. For purposes of the present disclosure, “dose dumping” refers to an unintended, rapid release of the entire amount or a significant fraction of the drug substance contained within a prescription drug product over a short or accelerated period of time. For purposes of abuse, alcohol-induced dose dumping may facilitate isolation or concentration of drug substances from a prescription drug product. Alternatively, dose dumping in the presence of alcohol may increase the ease with which a prescription drug product simply through the intake of an alcoholic beverage concommitantly with the prescription drug product. Moreover, alcohol-induced dose dumping may present safety issues outside the context of abuse. For example, a patient taking a prescription drug product for medicinal purposes may inadvertently cause delivery of a dose of drug substance that is too high or absorbed too quickly by self administering a drug product shortly before, simultaneously with or shortly after intake of an alcoholic beverage or another medicinal product containing alcohol (such as an over the counter cold or flu medicine). It has been reported that some modified-release oral dosage forms contain active drug substances and excipients that exhibit higher solubility in alcoholic solutions compared to water. Such products may exhibit a more rapid drug dissolution and release rate in the presence of ethanol.